Self-assembled Lanthanide luminescent Cyclen Complexes, from material to biological application

Abstract

The Thesis is entitled Self-assembled Lanthanide Luminescent Cyclen Complexes, from Material to Biological Application covers the formation of different Ln(III) cyclen based complexes and self-assembly and their applications in several fields. This includes the use of such complexes in solution and on solid surfaces (as thin films) in the monitoring of enzymatic reactions in real-time. The work carried out in this PhD study is divided into five chapters. The main focus of Chapter 1 is to give an introduction into the field of the luminescent sensing, with several examples of fluorescent sensors previously developed being featured and discussed. The unique photophysical properties that the lanthanide metal ions offer are then discussed, with several examples of lanthanide-based probes developed previously from the literature being featured, as well as those developed in the Gunnlaugsson group over the years are reviewed. In Chapter 2 the design, synthesis and photophysical evaluation of a novel cyclen based ligand is discussed. This ligand was designed with the view of developing a series of Ln(III) complexes, possessing the amphiphilicity required to be deposited these onto a quartz slides. These systems (both Eu(III) and Tb(III) based) form a self-assembly monolayer (SAM) on the water-air interface, and were then used to form Langmuir Blodgett (LB) films. The ability of these Ln(III) complexes, which were coordinatively unsaturated, to recognise and bind at the metal ion centre, amino acids was investigated by observing the changes in the lanthanide centred emission. The systems were indeed show to be able to discriminate between several amino acids in solution. The key result demonstrating that the complexes were able to act as probes for phosphorylated amino acids. The same investigation was performed for the Ln(III) complexes deposited onto the quartz slide, confirming the ability of the LB-slides to act as probes. In Chapter 3 a novel approach to monitor kinase assay activities is described. Using the Eu(III) complex developed in Chapter 2, an assay able to discriminate between ATP and ADP was developed. As was introduced in Chapter 2, the same experiment that showed this discrimination in solution, were also performed using SAM LB-films that had been deposited onto a quartz slide, forming, to the best of our knowledge, the first examples of a LB based assay for monitoring kinetic activities in real-time using such lanthanide iv complexes as SAMs. As before, this recognition process was monitored by observing the changes in the photophysical properties of the lanthanide complexes. Chapter 4 presents the wide field of applications of the Ln(III)-cyclen based complexes, by extending the application of such systems towards forming self-assemblies with other organic molecules in a host-guest manner. The main focus of the Chapter is to show the development of a self-assembled system in which a tripodal ligand based on the benzene1,3,5-tricarboxamide (BTA) motif, functionalised with terpyridine ligands, binds to the Ln(III) ion involved in the complex with heptadentate cyclen ligand which contains a strongly hydrophobic tail. The resulting aggregates were studied in solution through spectroscopic means and their mophological features were studied by SEM after deposition onto silica substrates, to inspect the photophysical and supramolecular properties of the system. Chapter 5 describes the synthesis, characterization and the potential of application of a new cyclen based ligand complexed with Tb(III) and Gd(III) ions, that could be applied in several research fields but the main focus is on the formation of Gd-49 and its potential application as MRI contrast agent. The work in this chapter is quite preliminary and the complexes were studied in solution using luminescent spectroscopic means and by SEM after deposition on silica substrates. Studies in vitro was performed using a novel microscopic technique called Two Photon Microscopy in order to investigate the ability of the complex to interact with the cell wall and act as a probe. The future work from this chapter will focus on exploring the properties of the Gd-system in NMRD measurements, which unfortunately could not be done during this PhD studies.